The explosion came as night fell and labourers working in central Quetta left for their homes on the outskirts of the city, which has frequently been targeted by Islamists and separatist insurgents.
"The death toll from the bus explosion is 11, while 22 people are injured," Akbar Hussain Durrani, home secretary of Balochistan province, told AFP.
A senior police official and a doctor at the city's main hospital confirmed the causalities.
Chaotic scenes unfolded in the emergency department of Provincial Sandeman Hospital as the dead and wounded were brought in, their blood staining stretchers and beds, as panicked relatives clamoured for help.
Durrani said the bus was loaded with labourers, but could not give any further details on how the explosion was detonated.
"We suspect somebody had hidden a bomb in the backside of the bus, but there is also a chance that somebody was maybe carrying it," Durrani said.
Senior police official Waheed Khatak told AFP the bomb exploded as the bus was driving near a fly-over in the Sariab road neighbourhood outside Quetta.
Pakistan's southwestern Baluchistan province, of which Quetta is the capital, is rife with Islamic, sectarian and separatist insurgencies.
Baloch separatists demanding more autonomy and control over gas and mineral resources have frequently attacked security forces, although there has been a lull this year after a police clampdown.
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